The purpose of this investigation is to study the mechanisms involved in the centrally mediated hypotensive action of alpha-methyldopa (alpha-MD) and mechanisms related to central cardiovascular control. This project is based on the hypothesis that alpha-MNE, the metabolite of alpha-MD, formed in the catecholaminergic terminals of the descending bulbospinal pathways, modulates the activity of sympathetic preganglionic neurons (SPGN). The inhibition of the activity of these neurons leads to a decrease in sympathetic output. Within the first year of the project it has been demonstrated that microiontophoretically applied alpha-MNE, NE and E inhibit the activity of SPGN (T2-T3 segments of the cord; cats anesthetized with a mixture of chloralose and urethane, paralyzed with gallamine and artificially respired) and that this action is mediated by catecholamine receptors of the alpha type. Alpha-MNE inhibition does not involve the release of endogenous NE because its action is preserved or even potentiated in reserpinized animals, and it is not limited to anesthetized animals because similar effects were observed in the cerveau isole preparation, without anesthesia. The research goals for the next year of this study are the following: Extend the above experiments on lower thoracic and lumbar segments of the cord, complete the comparison of the relative potencies of alpha-MNE and NE and investigate possible potentiating influence of microiontophoretically applied desipramine on the inhibitory effects of alpha-MNE and NE.